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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">actabiomedica</journal-id><journal-title-group><journal-title xml:lang="ru">Acta Biomedica Scientifica</journal-title><trans-title-group xml:lang="en"><trans-title>Acta Biomedica Scientifica</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2541-9420</issn><issn pub-type="epub">2587-9596</issn><publisher><publisher-name>Scientific Centre for Family Health and Human Reproduction Problems</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29413/ABS.2022-7.5-2.5</article-id><article-id custom-type="elpub" pub-id-type="custom">actabiomedica-3824</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ВНУТРЕННИЕ БОЛЕЗНИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>INTERNAL DISEASES</subject></subj-group></article-categories><title-group><article-title>Использование в клинической практике метода индуцированной мокроты у пациентов с бронхиальной астмой</article-title><trans-title-group xml:lang="en"><trans-title>Using induced sputum method in clinical practice in patients with bronchial asthma</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0952-6856</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Чулков</surname><given-names>В. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Chulkov</surname><given-names>V. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Чулков Василий Сергеевич – доктор медицинских наук, профессор кафедры факультетской терапии</p><p>454092, г. Челябинск, ул. Воровского, 64</p></bio><bio xml:lang="en"><p>Vasiliy S. Chulkov – Dr. Sc. (Med.), Professor at the Department of Intermediate-Level Therapy</p><p>Vorovskogo str. 64, Chelyabinsk 454092</p></bio><email xlink:type="simple">vschulkov@rambler.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1405-251X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Минина</surname><given-names>Е. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Minina</surname><given-names>E. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Минина Елена Евгеньевна – кандидат медицинских наук, старший лаборант кафедры факультетской педиатрии им. Н.С. Тюриной</p><p>454092, г. Челябинск, ул. Воровского, 64</p></bio><bio xml:lang="en"><p>Elena E. Minina – Cand. Sc. (Med.), Senior Teaching Assistant at the Department of Intermediate-Level Pediatrics named after N.S. Tuyrina</p><p>Vorovskogo str. 64, Chelyabinsk 454092</p></bio><email xlink:type="simple">eminina79@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1906-8465</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Медведева</surname><given-names>Л. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Medvedeva</surname><given-names>L V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Медведева Лариса Валентиновна – кандидат медицинских наук, доцент кафедры факультетской педиатрии им. Н.С. Тюриной</p><p>454092, г. Челябинск, ул. Воровского, 64</p></bio><bio xml:lang="en"><p>Larisa V. Medvedeva – Cand. Sc. (Med.), Associate Professor at the Department of Intermediate-Level Pediatrics named after N.S. Tuyrina</p><p>Vorovskogo str. 64, Chelyabinsk 454092</p></bio><email xlink:type="simple">larisa-medved@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБОУ ВО «Южно-Уральский государственный медицинский университет» Минздрава России</institution></aff><aff xml:lang="en"><institution>South Ural State Medical University</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2022</year></pub-date><pub-date pub-type="epub"><day>10</day><month>12</month><year>2022</year></pub-date><volume>7</volume><issue>5-2</issue><fpage>42</fpage><lpage>55</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Чулков В.С., Минина Е.Е., Медведева Л.В., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Чулков В.С., Минина Е.Е., Медведева Л.В.</copyright-holder><copyright-holder xml:lang="en">Chulkov V.S., Minina E.E., Medvedeva L.V.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.actabiomedica.ru/jour/article/view/3824">https://www.actabiomedica.ru/jour/article/view/3824</self-uri><abstract><p>В статье изложен обзор современных представлений о методе индуцированной мокроты, представлены подробное описание методики и протоколы получения мокроты у взрослых и детей, способы обработки полученного материала. В работе детально описываются особенности клеточного состава индуцированной мокроты у здоровых людей и у пациентов с бронхиальной астмой; подчёркивается значимость уровня эозинофилии как прогностического и диагностического критерия астмы; определяются функции других клеток индуцированной мокроты, таких как нейтрофилы, макрофаги, базофилы. Работа иллюстрирована фотографиями микроскопии мокроты. Помимо цитологии мокроты, подчёркивается возможность использования других методов исследования, таких как идентификация вирусных и бактериальных возбудителей, геномика, протеомика, липидомика, метаболомика, определение концентрации различных медиаторов в супернатанте мокроты. Даются представления о биохимических маркерах воспаления и ремоделирования дыхательных путей при астме, которые можно определить в мокроте (анафилатоксин С3а, кластерин, периостин, нейротоксин эозинофильного происхождения, фолликулин). Кроме того, в статье обобщены сведения о воспалительных фенотипах бронхиальной астмы, подчёркиваются их непостоянство и модификация в зависимости от периода заболевания, назначенного лечения, интеркуррентных респираторных инфекций, курения. Даны подробные характеристики эозинофильного, нейтрофильного, смешанного и малогранулоцитарного фенотипов бронхиальной астмы, отражены наиболее частые корреляции фенотипов с тяжестью и течением заболевания, параметрами функции лёгких и другими показателями. Описаны возможности использования метода индуцированной мокроты для комплексной оценки течения, контролируемости астмы и эффективности проводимой лекарственной терапии, а также для персонализированного подбора противовоспалительного препарата с учётом воспалительного фенотипа.</p></abstract><trans-abstract xml:lang="en"><p>This article presents an overview of modern statements of the induced sputum method; detailed description of the methods and protocols for taking sputum in adults and children, methods for processing the obtained substance. The paper describes in detail the features of the cellular composition of induced sputum in healthy individuals and in patients with bronchial asthma, emphasizes the importance of the eosinophilia level as a prognostic and diagnostic criterion of asthma and also determines the functions of other induced sputum cells such as neutrophils, macrophages, basophils. The article is illustrated with photographs of sputum microscopy. In addition to sputum cytology, we give accent to the possibility of using other research methods such as an identification of viral and bacterial pathogens, genomics, proteomics, lipidomics, metabolomics, determination of the concentration of various mediators in the sputum supernatant. The paper presents the ideas on biochemical inflammatory markers and remodelling of the respiratory tract in asthma, which can be determined in sputum (C3a anaphylatoxin, clusterin, periostin, eosinophil-derived neurotoxin, folliculin). In addition, we summarize the information on inflammatory phenotypes of bronchial asthma, emphasize their variability and modification depending on the period of the disease, prescribed treatment, intercurrent respiratory infections, and smoking. The article also presents detailed characteristics of eosinophilic, neutrophilic, mixed and small granulocyte phenotypes of bronchial asthma, and describes the most frequent correlations of phenotypes with the severity and course of the disease, with lung function parameters and other indicators. The paper gives an account of the possibilities of using the induced sputum method for a comprehensive assessment of the course, asthma controllability and the effectiveness of drug therapy, as well as for a personalized selection of an antiinflammatory drug considering the inflammatory phenotype.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>индуцированная мокрота</kwd><kwd>бронхиальная астма</kwd><kwd>воспалительный фенотип</kwd><kwd>эозинофил</kwd><kwd>нейтрофил</kwd><kwd>макрофаг</kwd></kwd-group><kwd-group xml:lang="en"><kwd>induced sputum</kwd><kwd>bronchial asthma</kwd><kwd>inflammatory phenotype</kwd><kwd>eosinophil</kwd><kwd>neutrophil</kwd><kwd>macrophage</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2021. URL: https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf [date of access: 26.03.2022].</mixed-citation><mixed-citation xml:lang="en">Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention. 2021. URL: https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf [date of access: 26.03.2022].</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Cao C, Li W, Hua W, Yan F, Zhang H, Huang H, et al. Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma. J Transl Med. 2017; 15(1): 171. doi: 10.1186/s12967-017-1264-y</mixed-citation><mixed-citation xml:lang="en">Cao C, Li W, Hua W, Yan F, Zhang H, Huang H, et al. Proteomic analysis of sputum reveals novel biomarkers for various presentations of asthma. J Transl Med. 2017; 15(1): 171. doi: 10.1186/s12967-017-1264-y</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Inoue H, Ito I, Niimi A, Matsumoto H, Matsuoka H, Jinnai M, et al. CT-assessed large airway involvement and lung function decline in eosinophilic asthma: The association between induced sputum eosinophil differential counts and airway remodeling. J Asthma. 2016; 53(9): 914-921. doi: 10.3109/02770903.2016.1167903</mixed-citation><mixed-citation xml:lang="en">Inoue H, Ito I, Niimi A, Matsumoto H, Matsuoka H, Jinnai M, et al. CT-assessed large airway involvement and lung function decline in eosinophilic asthma: The association between induced sputum eosinophil differential counts and airway remodeling. J Asthma. 2016; 53(9): 914-921. doi: 10.3109/02770903.2016.1167903</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Ntontsi P, Loukides S, Bakakos P, Kostikas K, Papatheodorou G, Papathanassiou E, et al. Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes. Allergy. 2017; 72(11): 1761-1767. doi: 10.1111/all.13184</mixed-citation><mixed-citation xml:lang="en">Ntontsi P, Loukides S, Bakakos P, Kostikas K, Papatheodorou G, Papathanassiou E, et al. Clinical, functional and inflammatory characteristics in patients with paucigranulocytic stable asthma: Comparison with different sputum phenotypes. Allergy. 2017; 72(11): 1761-1767. doi: 10.1111/all.13184</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Мизерницкий Ю.Л., Мельникова И.М., Павленко В.А. Меполизумаб в терапии бронхиальной астмы у детей. Медицинский совет. 2020; (1): 81-86. doi: 10.21518/2079-701X-2020-1-81-86</mixed-citation><mixed-citation xml:lang="en">Mizernitskiy YuL, Mel’nikova IM, Pavlenko VA. Mepolizumab in the treatment of bronchial asthma in children. Medical Council. 2020; (1): 81-86. (In Russ.). doi: 10.21518/2079-701X-2020-1-81-86</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Lacwik P, Kupczyk M. Asthma phenotype overlap: More may be less. J Allergy Clin Immunol Pract. 2021; 9(1): 363-364. doi: 10.1016/j.jaip.2020.10.032</mixed-citation><mixed-citation xml:lang="en">Lacwik P, Kupczyk M. Asthma phenotype overlap: More may be less. J Allergy Clin Immunol Pract. 2021; 9(1): 363-364. doi: 10.1016/j.jaip.2020.10.032</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Papi A, Brightling С, Pedersen S, Reddel H. Asthma. Review Lancet. 2018; 391(10122): 783-800. doi: 10.1016/S0140-6736(17)33311-1</mixed-citation><mixed-citation xml:lang="en">Papi A, Brightling С, Pedersen S, Reddel H. Asthma. Review Lancet. 2018; 391(10122): 783-800. doi: 10.1016/S0140-6736(17)33311-1</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Тютина О.С., Смирнова С.В., Смольникова М.В., Ильенкова Н.А. Клинико-иммунологические особенности атопической бронхиальной астмы в зависимости от уровня контроля над заболеванием у детей. Acta biomedica scientifica. 2012; 3(2): 204-207.</mixed-citation><mixed-citation xml:lang="en">Tyutina OS, Smirnova SV, Smolnikova MV, Ilyenkova NA. Clinical immunological peculiaraties of atopic bronchial asthma depending from the level of control over the disease in children. Acta biomedica scientifica. 2012; 3(2): 204-207. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Weiszhar Z, Horvath I. Induced sputum analysis: step by step. Breathe. 2013; 9: 300-306. doi: 10.1183/20734735.042912</mixed-citation><mixed-citation xml:lang="en">Weiszhar Z, Horvath I. Induced sputum analysis: step by step. Breathe. 2013; 9: 300-306. doi: 10.1183/20734735.042912</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Guiot J, Demarche S, Henket M, Paulus V, Graff S, Schleich F, et al. Methodology for sputum induction and laboratory processing. J Vis Exp. 2017; 130: 56612. doi: 10.3791/56612</mixed-citation><mixed-citation xml:lang="en">Guiot J, Demarche S, Henket M, Paulus V, Graff S, Schleich F, et al. Methodology for sputum induction and laboratory processing. J Vis Exp. 2017; 130: 56612. doi: 10.3791/56612</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Куличков В.И., Мизерницкий Ю.Л., Рыбакова О.Г., Жаков Я.И., Минина Е.Е. Способ получения индуцированной мокроты у детей для оценки степени и характера воспаления слизистой бронхов: Патент № 2364341 Рос. Федерация; МПК A61B 10/00 (2006.01), G01N 33/53 (2006.01). № 2008116364; заявл. 24.04.2008; опубл. 20.08.2009. Бюл. № 23.</mixed-citation><mixed-citation xml:lang="en">Kulichkov VI, Mizernitsky YuL, Rybakova OG, Zhakov YaI, Minina EE. A method for obtaining induced sputum in children to assess the degree and nature of inflammation of the bronchial mucosa: Patent No. 2364341 of the Russian Federation. 2009; (23). (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Kansal P, Nandan D, Agarwal S, Patharia N, Arya N. Correlation of induced sputum eosinophil levels with clinical parameters in mild and moderate persistent asthma in children aged 7–18 years. J Asthma. 2018; 55(4): 385-390. doi: 10.1080/02770903.2017.1338725</mixed-citation><mixed-citation xml:lang="en">Kansal P, Nandan D, Agarwal S, Patharia N, Arya N. Correlation of induced sputum eosinophil levels with clinical parameters in mild and moderate persistent asthma in children aged 7–18 years. J Asthma. 2018; 55(4): 385-390. doi: 10.1080/02770903.2017.1338725</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Жаков Я.И., Минина Е.Е., Медведева Л.В. Воспалительные фенотипы при обострении вирус-индуцированной бронхиальной астмы у детей и их изменение в динамике. Российский вестник перинатологии и педиатрии. 2015; 60(4): 229.</mixed-citation><mixed-citation xml:lang="en">Zhakov YI, Minina EE, Medvedeva LV. Inflammatory phenotypes during exacerbation of virus-induced bronchial asthma in children and their changes over time. Russian Bulletin of Perinatology and Pediatrics. 2015; 60(4): 229. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Жаков Я.И., Минина Е.Е., Медведева Л.В. Влияние тилорона на цитоиммунологические показатели индуцированной мокроты и частоту обострений бронхиальной астмы, обусловленных респираторной вирусной инфекцией. Российский вестник перинатологии и педиатрии. 2017; 62(2): 65-70. doi: 10.21508/1027-4065-2017-62-2-65-70</mixed-citation><mixed-citation xml:lang="en">Zhakov YI, Minina EE, Medvedeva LV. The effect of tilorone on the cytoimmunological parameters of induced sputum and on the frequency of asthma exacerbations caused by respiratory viral infection. Russian Bulletin of Perinatology and Pediatrics. 2017; 62(2): 65-70. (In Russ.). doi: 10.21508/1027-4065-2017-62-2-65-70</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Ghebre MA, Pang PH, Desai D, Hargadon B, Newby C, Woods J, et al. Severe exacerbations in moderate-to-severe asthmatics are associated with increased pro-inflammatory and type 1 mediators in sputum and serum. BMC Pulm Med. 2019; 19(1): 144. doi: 10.1186/s12890-019-0906-7</mixed-citation><mixed-citation xml:lang="en">Ghebre MA, Pang PH, Desai D, Hargadon B, Newby C, Woods J, et al. Severe exacerbations in moderate-to-severe asthmatics are associated with increased pro-inflammatory and type 1 mediators in sputum and serum. BMC Pulm Med. 2019; 19(1): 144. doi: 10.1186/s12890-019-0906-7</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Bickerman HA, Sproul EE, Barach AL. An aerosol method of producing bronchial secretions in human subjects: A clinical technique for the detection of lung cancer. Dis Chest. 1958; 33: 347-362.</mixed-citation><mixed-citation xml:lang="en">Bickerman HA, Sproul EE, Barach AL. An aerosol method of producing bronchial secretions in human subjects: A clinical technique for the detection of lung cancer. Dis Chest. 1958; 33: 347-362.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Pin I, Gibson PG, Kolendowicz R, Girgis-Gabardo A, Denburg JA, Hargreave FE, et al. Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax. 1992; 47(1): 25-29. doi: 10.1136/thx.47.1.25</mixed-citation><mixed-citation xml:lang="en">Pin I, Gibson PG, Kolendowicz R, Girgis-Gabardo A, Denburg JA, Hargreave FE, et al. Use of induced sputum cell counts to investigate airway inflammation in asthma. Thorax. 1992; 47(1): 25-29. doi: 10.1136/thx.47.1.25</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Popov TA, Pizzichini MM, Pizzichini E, Kolendowicz R, Punthakee Z, Dolovich J, et al. Some technical factors influencing the induction of sputum for cell analysis. Eur Respir J. 1995; 8(4): 559-565. doi: 10.1183/09031936.95.08040559</mixed-citation><mixed-citation xml:lang="en">Popov TA, Pizzichini MM, Pizzichini E, Kolendowicz R, Punthakee Z, Dolovich J, et al. Some technical factors influencing the induction of sputum for cell analysis. Eur Respir J. 1995; 8(4): 559-565. doi: 10.1183/09031936.95.08040559</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Djukanović R, Sterk PJ, Fahy JV. Standardised methodology of sputum induction and processing. Eur Respir J Suppl. 2002; 37: 1s-2s. doi: 10.1183/09031936.02.00000102</mixed-citation><mixed-citation xml:lang="en">Djukanović R, Sterk PJ, Fahy JV. Standardised methodology of sputum induction and processing. Eur Respir J Suppl. 2002; 37: 1s-2s. doi: 10.1183/09031936.02.00000102</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Paggiaro PL, Chanez P, Holz O, Indz PW, Djukanovic R, Maestrelli P, et al. Sputum induction. Eur Respir J Suppl. 2002; 37: 3s-8s. doi: 10.1183/09031936.02.00000302</mixed-citation><mixed-citation xml:lang="en">Paggiaro PL, Chanez P, Holz O, Indz PW, Djukanovic R, Maestrelli P, et al. Sputum induction. Eur Respir J Suppl. 2002; 37: 3s-8s. doi: 10.1183/09031936.02.00000302</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Pizzichini E, Pizzichini MM, Leigh R, Djukanović R, Sterk PJ. Safety of sputum induction. Eur Respir J Suppl. 2002; 37: 9s-18s. doi: 10.1183/09031936.02.00000902</mixed-citation><mixed-citation xml:lang="en">Pizzichini E, Pizzichini MM, Leigh R, Djukanović R, Sterk PJ. Safety of sputum induction. Eur Respir J Suppl. 2002; 37: 9s-18s. doi: 10.1183/09031936.02.00000902</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Efthimiadis A, Spanevello A, Hamid Q, Kelly MM, Linden M, Louis R, et al. Methods of sputum processing for cell counts, immunohistochemistry and in situ hibridisation. Eur Respir J Suppl. 2002; 37: 19s-23s. doi: 10.1183/09031936.02.00001902</mixed-citation><mixed-citation xml:lang="en">Efthimiadis A, Spanevello A, Hamid Q, Kelly MM, Linden M, Louis R, et al. Methods of sputum processing for cell counts, immunohistochemistry and in situ hibridisation. Eur Respir J Suppl. 2002; 37: 19s-23s. doi: 10.1183/09031936.02.00001902</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Kelly MM, Keatings V, Leigh R, Peterson C, Shute J, Venge P, et al. Analysis of fluid- phase mediators. Eur Respir J Suppl. 2002; 37: 24s-39s. doi: 10.1183/09031936.02.00002402</mixed-citation><mixed-citation xml:lang="en">Kelly MM, Keatings V, Leigh R, Peterson C, Shute J, Venge P, et al. Analysis of fluid- phase mediators. Eur Respir J Suppl. 2002; 37: 24s-39s. doi: 10.1183/09031936.02.00002402</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Gibson PG, Grootendor DC, Henry RL, Pin I, Rytila PL, Wark P, et al. Sputum induction in children. Eur Respir J Suppl. 2002; 37: 44s-46s. doi: 10.1183/09031936.02.00004402</mixed-citation><mixed-citation xml:lang="en">Gibson PG, Grootendor DC, Henry RL, Pin I, Rytila PL, Wark P, et al. Sputum induction in children. Eur Respir J Suppl. 2002; 37: 44s-46s. doi: 10.1183/09031936.02.00004402</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Koc-Günel S, Schubert R, Zielen S, Rosewich M. Cell distribution and cytokine levels in induced sputum from healthy subjects and patients with asthma after using different nebulizer techniques. BMC Pulm Med. 2018; 18(1): 115. doi: 10.1186/s12890-018-0683-8</mixed-citation><mixed-citation xml:lang="en">Koc-Günel S, Schubert R, Zielen S, Rosewich M. Cell distribution and cytokine levels in induced sputum from healthy subjects and patients with asthma after using different nebulizer techniques. BMC Pulm Med. 2018; 18(1): 115. doi: 10.1186/s12890-018-0683-8</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Kasaian MT, Lee J, Brennan A, Danto SI, Black KE, Fitz L, et al. Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics. Clin Exp Allergy. 2018; 48(7): 814-824. doi: 10.1111/cea.13151</mixed-citation><mixed-citation xml:lang="en">Kasaian MT, Lee J, Brennan A, Danto SI, Black KE, Fitz L, et al. Proteomic analysis of serum and sputum analytes distinguishes controlled and poorly controlled asthmatics. Clin Exp Allergy. 2018; 48(7): 814-824. doi: 10.1111/cea.13151</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Bush A. Translating asthma: Dissecting the role of metabolomics, genomics and personalized medicine. Indian J Pediatr. 2018; 85(8): 643-650. doi: 10.1007/s12098-017-2520-0</mixed-citation><mixed-citation xml:lang="en">Bush A. Translating asthma: Dissecting the role of metabolomics, genomics and personalized medicine. Indian J Pediatr. 2018; 85(8): 643-650. doi: 10.1007/s12098-017-2520-0</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Santos A, Pité H, Chaves-Loureiro C, Rocha S, Taborda-Barata L. Metabolic phenotypes in asthmatic adults: Relationship with inflammatory and clinical phenotypes and prognostic. Review Metabolites. 2021; 11(8): 534. doi: 10.3390/metabo11080534</mixed-citation><mixed-citation xml:lang="en">Santos A, Pité H, Chaves-Loureiro C, Rocha S, Taborda-Barata L. Metabolic phenotypes in asthmatic adults: Relationship with inflammatory and clinical phenotypes and prognostic. Review Metabolites. 2021; 11(8): 534. doi: 10.3390/metabo11080534</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Костина Е.М., Трушина Е.Ю. Роль нейтрофильной эластазы и IL-8 в патогенезе типа воспаления у больных неаллергической бронхиальной астмой. Журнал научных статей Здоровье и образование в XXI веке. 2019; 21(3): 22-26. doi: 10.26787/nydha-2226-7425-2019-21-3-22-26</mixed-citation><mixed-citation xml:lang="en">Kostina EM, Trushina EYu. Neutrophilic elastase and IL-8 role in the inflammation type pathogenesis in patients with nonallergical bronchial asthma. The Journal of Scientific Articles. Health and Millenium Education. 2019; 21(3): 22-26. (In Russ.). doi: 10.26787/nydha-2226-7425-2019-21-3-22-26</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Rytilä P, Pelkonen AS, Metso T, Nikander K, Haahtela T, Turpeinen M. Induced sputum in children with newly diagnosed mild asthma: the effect of 6 months of treatment with budesonide or disodium cromoglycate. Allergy. 2004; 59(8): 839-844. doi: 10.1111/j.1398-9995.2004.00504.x</mixed-citation><mixed-citation xml:lang="en">Rytilä P, Pelkonen AS, Metso T, Nikander K, Haahtela T, Turpeinen M. Induced sputum in children with newly diagnosed mild asthma: the effect of 6 months of treatment with budesonide or disodium cromoglycate. Allergy. 2004; 59(8): 839-844. doi: 10.1111/j.1398-9995.2004.00504.x</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Luo W, Chen Q, Chen R, Xie Y, Wang H, Lai K. Reference value of induced sputum cell counts and its relationship with age in healthy adults in Guangzhou, Southern China. Clin Respir J. 2018; 12(3): 1160-1165. doi: 10.1111/crj.12645</mixed-citation><mixed-citation xml:lang="en">Luo W, Chen Q, Chen R, Xie Y, Wang H, Lai K. Reference value of induced sputum cell counts and its relationship with age in healthy adults in Guangzhou, Southern China. Clin Respir J. 2018; 12(3): 1160-1165. doi: 10.1111/crj.12645</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Demarche S, Schleich F, Henket M, Paulus V, Van Hees TV, Louis R. Detailed analysis of sputum and systemic inflammation in asthma phenotypes: Are paucigranulocytic asthmatics really non-inflammatory? BMC Pulmonary Medicine. 2016; 16: 46. doi: 10.1186/s12890-016-0208-2</mixed-citation><mixed-citation xml:lang="en">Demarche S, Schleich F, Henket M, Paulus V, Van Hees TV, Louis R. Detailed analysis of sputum and systemic inflammation in asthma phenotypes: Are paucigranulocytic asthmatics really non-inflammatory? BMC Pulmonary Medicine. 2016; 16: 46. doi: 10.1186/s12890-016-0208-2</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Mahabee-Gittens EM, Merianos AL, Fulkerson PC, Stone L, Matt GE. The association of environmental tobacco smoke exposure and inflammatory markers in hospitalized children. Int J Environ Res Public Health. 2019; 16(23): 4625. doi: 10.3390/ijerph16234625</mixed-citation><mixed-citation xml:lang="en">Mahabee-Gittens EM, Merianos AL, Fulkerson PC, Stone L, Matt GE. The association of environmental tobacco smoke exposure and inflammatory markers in hospitalized children. Int J Environ Res Public Health. 2019; 16(23): 4625. doi: 10.3390/ijerph16234625</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Zacharasiewicz A, Wilson N, Lex C, Erin EM, Li AM, Hansel T, et al. Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children. Am J Respir Crit Care Med. 2005; 171(10): 1077-1082. doi: 10.1164/rccm.200409-1242OC</mixed-citation><mixed-citation xml:lang="en">Zacharasiewicz A, Wilson N, Lex C, Erin EM, Li AM, Hansel T, et al. Clinical use of noninvasive measurements of airway inflammation in steroid reduction in children. Am J Respir Crit Care Med. 2005; 171(10): 1077-1082. doi: 10.1164/rccm.200409-1242OC</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Carr TF, Zeki AA, Kraft M. Eosinophilic and noneosinophilic asthma. Respir Crit Care Med. 2018; 197(1): 22-37. doi: 10.1164/rccm.201611-2232PP</mixed-citation><mixed-citation xml:lang="en">Carr TF, Zeki AA, Kraft M. Eosinophilic and noneosinophilic asthma. Respir Crit Care Med. 2018; 197(1): 22-37. doi: 10.1164/rccm.201611-2232PP</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Suzuki Y, Wakahara K, Nishio T, Ito S, Hasegawa Y. Airway basophils are increased and activated in eosinophilic asthma. Allergy. 2017; 72(10): 1532-1539. doi: 10.1111/all.13197</mixed-citation><mixed-citation xml:lang="en">Suzuki Y, Wakahara K, Nishio T, Ito S, Hasegawa Y. Airway basophils are increased and activated in eosinophilic asthma. Allergy. 2017; 72(10): 1532-1539. doi: 10.1111/all.13197</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Fux M, von Garnier C. Sputum basophils and asthma diagnosis: dawn of a new era? Allergy. 2017; 72(10): 1437-1439. doi: 10.1111/all.13214</mixed-citation><mixed-citation xml:lang="en">Fux M, von Garnier C. Sputum basophils and asthma diagnosis: dawn of a new era? Allergy. 2017; 72(10): 1437-1439. doi: 10.1111/all.13214</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Поспелова С.Н., Собченко С.А., Кравцов В.Ю. Возможности цитологических и иммуноцитохимических показателей индуцированной мокроты в оценке воспаления дыхательных путей при разных уровнях контроля бронхиальной астмы. Вестник Северо-Западного государственного медицинского университета им. И.И. Мечникова. 2015; 7(2): 68-73.</mixed-citation><mixed-citation xml:lang="en">Pospelova SN, Sobchenko SA, Kravtsov VYu. Possibilities of cytological and immunocytochemical markers of induced sputum in the evaluation of airway inflammation in patients with different levels of asthma control. Herald of North-Western State Medical University named after I.I. Mechnikov. 2015; 7(2): 68-73. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Pretolani M, Soussan D, Poirier I, Thabut G, Aubier M. Clinical and biological characteristics of the French COBRA cohort of adult subjects with asthma. Eur Respir J. 2017; 50(2): 1700019. doi: 10.1183/13993003.00019-2017</mixed-citation><mixed-citation xml:lang="en">Pretolani M, Soussan D, Poirier I, Thabut G, Aubier M. Clinical and biological characteristics of the French COBRA cohort of adult subjects with asthma. Eur Respir J. 2017; 50(2): 1700019. doi: 10.1183/13993003.00019-2017</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Lima-Matos A, Ponte EV, de Jesus JPV, Almeida PCA, Lima VB, Kwon N, et al. Eosinophilic asthma, according to a blood eosinophil criterion, is associated with disease severity and lack of control among underprivileged urban Brazilians. Respir Med. 2018; 145: 95-100. doi: 10.1016/j.rmed.2018.10.025</mixed-citation><mixed-citation xml:lang="en">Lima-Matos A, Ponte EV, de Jesus JPV, Almeida PCA, Lima VB, Kwon N, et al. Eosinophilic asthma, according to a blood eosinophil criterion, is associated with disease severity and lack of control among underprivileged urban Brazilians. Respir Med. 2018; 145: 95-100. doi: 10.1016/j.rmed.2018.10.025</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Guo Y, Zou Y, Zhai J, Li J, Liu J, Ma C, et al. Phenotypes of the inflammatory cells in the induced sputum from young children or infants with recurrent wheezing. Pediatr Res. 2019; 85(4): 489-493. doi: 10.1038/s41390-018-0268-5</mixed-citation><mixed-citation xml:lang="en">Guo Y, Zou Y, Zhai J, Li J, Liu J, Ma C, et al. Phenotypes of the inflammatory cells in the induced sputum from young children or infants with recurrent wheezing. Pediatr Res. 2019; 85(4): 489-493. doi: 10.1038/s41390-018-0268-5</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Petsky HL, Li A, Chang AB. Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults. Cochrane Database Syst Rev. 2017; 8(8): CD005603. doi: 10.1002/14651858.CD005603.pub3</mixed-citation><mixed-citation xml:lang="en">Petsky HL, Li A, Chang AB. Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults. Cochrane Database Syst Rev. 2017; 8(8): CD005603. doi: 10.1002/14651858.CD005603.pub3</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Moore WC, Hastie AT, Li X, Li H, Busse WW, Jarjour NN, et al. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol. 2014; 133(6): 1557-1563.e5. doi: 10.1016/j.jaci.2013.10.011</mixed-citation><mixed-citation xml:lang="en">Moore WC, Hastie AT, Li X, Li H, Busse WW, Jarjour NN, et al. Sputum neutrophil counts are associated with more severe asthma phenotypes using cluster analysis. J Allergy Clin Immunol. 2014; 133(6): 1557-1563.e5. doi: 10.1016/j.jaci.2013.10.011</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Chung KF. Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies. J Intern Med. 2016; 279(2): 192-204. doi: 10.1111/joim.12382</mixed-citation><mixed-citation xml:lang="en">Chung KF. Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies. J Intern Med. 2016; 279(2): 192-204. doi: 10.1111/joim.12382</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Ray A, Kolls JK. Neutrophilic inflammation in asthma and association with disease severity. Trends Immunol. 2017; 38(12): 942-954. doi: 10.1016/j.it.2017.07.003</mixed-citation><mixed-citation xml:lang="en">Ray A, Kolls JK. Neutrophilic inflammation in asthma and association with disease severity. Trends Immunol. 2017; 38(12): 942-954. doi: 10.1016/j.it.2017.07.003</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Van der Veen TA, de Groot LES, Melgert BN. The different faces of the macrophage in asthma. Curr Opin Pulm Med. 2020; 26(1): 62-68. doi: 10.1097/MCP.0000000000000647</mixed-citation><mixed-citation xml:lang="en">Van der Veen TA, de Groot LES, Melgert BN. The different faces of the macrophage in asthma. Curr Opin Pulm Med. 2020; 26(1): 62-68. doi: 10.1097/MCP.0000000000000647</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011; 11(11): 723-737. doi: 10.1038/nri3073</mixed-citation><mixed-citation xml:lang="en">Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol. 2011; 11(11): 723-737. doi: 10.1038/nri3073</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Kulkarni N, Kantar A, Costella S, Ragazzo V, Piacentini G, Boner A, et al. Macrophage phagocytosis and allergen avoidance in children with asthma. Front Pediatr. 2018; 6: 206. doi: 10.3389/fped.2018.00206</mixed-citation><mixed-citation xml:lang="en">Kulkarni N, Kantar A, Costella S, Ragazzo V, Piacentini G, Boner A, et al. Macrophage phagocytosis and allergen avoidance in children with asthma. Front Pediatr. 2018; 6: 206. doi: 10.3389/fped.2018.00206</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Barril S, Sebastián L, Cotta G, Crespo A, Mateus E, Torrejón M, et al. Utility of induced sputum in routine clinical practice. Arch Bronconeumol. 2016; 52(5): 250-255. doi: 10.1016/j arbres.2015.10.002</mixed-citation><mixed-citation xml:lang="en">Barril S, Sebastián L, Cotta G, Crespo A, Mateus E, Torrejón M, et al. Utility of induced sputum in routine clinical practice. Arch Bronconeumol. 2016; 52(5): 250-255. doi: 10.1016/j.arbres.2015.10.002</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Zhang J, Ding YL, Chen YH, Yao WZ. Changes of C3a in induced sputum in patients with asthma. Nan Fang Yi Ke Da Xue Xue Bao. 2015; 35(1): 51-55.</mixed-citation><mixed-citation xml:lang="en">Zhang J, Ding YL, Chen YH, Yao WZ. Changes of C3a in induced sputum in patients with asthma. Nan Fang Yi Ke Da Xue Xue Bao. 2015; 35(1): 51-55.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Jia G, Erickson RW, Choy DF, Mosesova S, Wu LC, Solberg OD, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol. 2012; 130(3): 647-654.e10. doi: 10.1016/j.jaci.2012.06.025</mixed-citation><mixed-citation xml:lang="en">Jia G, Erickson RW, Choy DF, Mosesova S, Wu LC, Solberg OD, et al. Periostin is a systemic biomarker of eosinophilic airway inflammation in asthmatic patients. J Allergy Clin Immunol. 2012; 130(3): 647-654.e10. doi: 10.1016/j.jaci.2012.06.025</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Bobolea I, Barranco P, Del Pozo V, Romero D, Sanz V, López-Carrasco V, et al. Sputum periostin in patients with different severe asthma phenotypes. Allergy. 2015; 70(5): 540-546. doi: 10.1111/all.12580</mixed-citation><mixed-citation xml:lang="en">Bobolea I, Barranco P, Del Pozo V, Romero D, Sanz V, López- Carrasco V, et al. Sputum periostin in patients with different severe asthma phenotypes. Allergy. 2015; 70(5): 540-546. doi: 10.1111/all.12580</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Refaat М, Sayed E, El-Fattah W, Elbanna A, Sayed H. Relationship between sputum periostin level and inflammatory asthma phenotypes in Egyptian patients. J Asthma. 2021; 58(10): 1285-1291. doi: 10.1080/02770903.2020.1786111</mixed-citation><mixed-citation xml:lang="en">Refaat М, Sayed E, El-Fattah W, Elbanna A, Sayed H. Relationship between sputum periostin level and inflammatory asthma phenotypes in Egyptian patients. J Asthma. 2021; 58(10): 1285-1291. doi: 10.1080/02770903.2020.1786111</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Sol IS, Kim YH, Park YA, Lee KE, Hong JY, Kim MN, et al. Relationship between sputum clusterin levels and childhood asthma. Clin Exp Allergy. 2016; 46(5): 688-695. doi: 10.1111/cea.12686</mixed-citation><mixed-citation xml:lang="en">Sol IS, Kim YH, Park YA, Lee KE, Hong JY, Kim MN, et al. Relationship between sputum clusterin levels and childhood asthma. Clin Exp Allergy. 2016; 46(5): 688-695. doi: 10.1111/cea.12686</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Kim SY, Kim JD, Sol IS, Kim MJ, Kim MN, Hong JY, et al. Sputum TWEAK expression correlates with severity and degree of control in non-eosinophilic childhood asthma. Pediatr Allergy Immunol. 2018; 29(1): 42-49. doi: 10.1111/pai.12827</mixed-citation><mixed-citation xml:lang="en">Kim SY, Kim JD, Sol IS, Kim MJ, Kim MN, Hong JY, et al. Sputum TWEAK expression correlates with severity and degree of control in non-eosinophilic childhood asthma. Pediatr Allergy Immunol. 2018; 29(1): 42-49. doi: 10.1111/pai.12827</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Kim SH. Blood molecular biomarkers of the inflammatory phenotypes of asthma. Editorial Korean J Intern Med. 2020; 35(4): 857-860. doi: 10.3904/kjim.2020.296</mixed-citation><mixed-citation xml:lang="en">Kim SH. Blood molecular biomarkers of the inflammatory phenotypes of asthma. Editorial Korean J Intern Med. 2020; 35(4): 857-860. doi: 10.3904/kjim.2020.296</mixed-citation></citation-alternatives></ref><ref id="cit57"><label>57</label><citation-alternatives><mixed-citation xml:lang="ru">Kim SY, Jung HW, Kim М, Moon JY, Ban GY, Kim SJ, et al. Ceramide/sphingosine-1-phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma. Allergy. 2020; 75(8): 1991-2004. doi: 10.1111/all.14236</mixed-citation><mixed-citation xml:lang="en">Kim SY, Jung HW, Kim М, Moon JY, Ban GY, Kim SJ, et al. Ceramide/sphingosine-1-phosphate imbalance is associated with distinct inflammatory phenotypes of uncontrolled asthma. Allergy. 2020; 75(8): 1991-2004. doi: 10.1111/all.14236</mixed-citation></citation-alternatives></ref><ref id="cit58"><label>58</label><citation-alternatives><mixed-citation xml:lang="ru">Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019; 56(2): 219-233. doi: 10.1007/s12016-018-8712-1</mixed-citation><mixed-citation xml:lang="en">Kuruvilla ME, Lee FE, Lee GB. Understanding asthma phenotypes, endotypes, and mechanisms of disease. Clin Rev Allergy Immunol. 2019; 56(2): 219-233. doi: 10.1007/s12016-018-8712-1</mixed-citation></citation-alternatives></ref><ref id="cit59"><label>59</label><citation-alternatives><mixed-citation xml:lang="ru">Conrad LA, Cabana MD, Rastogi D, Bush A. Defining pediatric asthma: Phenotypes to endotypes and beyond. Review Pediatr Res. 2021; 90(1): 45-51. doi: 10.1038/s41390-020-01231-6</mixed-citation><mixed-citation xml:lang="en">Conrad LA, Cabana MD, Rastogi D, Bush A. Defining pediatric asthma: Phenotypes to endotypes and beyond. Review Pediatr Res. 2021; 90(1): 45-51. doi: 10.1038/s41390-020-01231-6</mixed-citation></citation-alternatives></ref><ref id="cit60"><label>60</label><citation-alternatives><mixed-citation xml:lang="ru">Côté А, Godbout K, Boulet LP. The management of severe asthma in 2020. Review Biochem Pharmacol. 2020; 179: 114112. doi: 10.1016/j.bcp.2020.114112</mixed-citation><mixed-citation xml:lang="en">Côté А, Godbout K, Boulet LP. The management of severe asthma in 2020. Review Biochem Pharmacol. 2020; 179: 114112. doi: 10.1016/j.bcp.2020.114112</mixed-citation></citation-alternatives></ref><ref id="cit61"><label>61</label><citation-alternatives><mixed-citation xml:lang="ru">Ricciardolo F, Bertolini F, Carriero V, Sprio АЕ. Asthma phenotypes and endotypes. Minerva Med. 2021; 112(5): 547-563. doi: 10.23736/S0026-4806.21.07498-X</mixed-citation><mixed-citation xml:lang="en">Ricciardolo F, Bertolini F, Carriero V, Sprio АЕ. Asthma phenotypes and endotypes. Minerva Med. 2021; 112(5): 547-563. doi: 10.23736/S0026-4806.21.07498-X</mixed-citation></citation-alternatives></ref><ref id="cit62"><label>62</label><citation-alternatives><mixed-citation xml:lang="ru">Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: Assessment and identification using induced sputum. Respirology. 2006; 11; 54-61. doi: 10.1111/j.1440-1843.2006.00784.x</mixed-citation><mixed-citation xml:lang="en">Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: Assessment and identification using induced sputum. Respirology. 2006; 11; 54-61. doi: 10.1111/j.1440-1843.2006.00784.x</mixed-citation></citation-alternatives></ref><ref id="cit63"><label>63</label><citation-alternatives><mixed-citation xml:lang="ru">Taylor SL, Leong L, Choo JM, Wesselingh S, Yang IA, Upham JW. Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology. J Allergy Clin Immunol. 2018; 141(1): 94-103.e15. doi: 10.1016/j.jaci.2017.03.044</mixed-citation><mixed-citation xml:lang="en">Taylor SL, Leong L, Choo JM, Wesselingh S, Yang IA, Upham JW. Inflammatory phenotypes in patients with severe asthma are associated with distinct airway microbiology. J Allergy Clin Immunol. 2018; 141(1): 94-103.e15. doi: 10.1016/j.jaci.2017.03.044</mixed-citation></citation-alternatives></ref><ref id="cit64"><label>64</label><citation-alternatives><mixed-citation xml:lang="ru">Nelson RK, Bush A, Stokes J, Nair P, Akuthota P. Eosinophilic asthma. J Allergy Clin Immunol Pract. 2020; 8(2): 465-473. doi: 10.1016/j.jaip.2019.11.024</mixed-citation><mixed-citation xml:lang="en">Nelson RK, Bush A, Stokes J, Nair P, Akuthota P. Eosinophilic asthma. J Allergy Clin Immunol Pract. 2020; 8(2): 465-473. doi: 10.1016/j.jaip.2019.11.024</mixed-citation></citation-alternatives></ref><ref id="cit65"><label>65</label><citation-alternatives><mixed-citation xml:lang="ru">Hinks TS, Levine SJ, Brusselle GG. Treatment options in type-2 low asthma. Review Eur Respir J. 2020; 57b(1): 2000528. doi: 10.1183/13993003.00528-2020</mixed-citation><mixed-citation xml:lang="en">Hinks TS, Levine SJ, Brusselle GG. Treatment options in type-2 low asthma. Review Eur Respir J. 2020; 57b(1): 2000528. doi: 10.1183/13993003.00528-2020</mixed-citation></citation-alternatives></ref><ref id="cit66"><label>66</label><citation-alternatives><mixed-citation xml:lang="ru">Schoettler N, Strek ME. Recent advances in severe asthma: From phenotypes to personalized medicine. Review Chest. 2020; 157(3): 516-528. doi: 10.1016/j.chest.2019.10.009</mixed-citation><mixed-citation xml:lang="en">Schoettler N, Strek ME. Recent advances in severe asthma: From phenotypes to personalized medicine. Review Chest. 2020; 157(3): 516-528. doi: 10.1016/j.chest.2019.10.009</mixed-citation></citation-alternatives></ref><ref id="cit67"><label>67</label><citation-alternatives><mixed-citation xml:lang="ru">Suárez-Cuartín G, Crespo A, Mateus E, Torrejón M, Giner J, Belda A, et al. Variability in asthma inflammatory phenotype in induced sputum. Frequency and causes. Arch Bronconeumol. 2016; 52: 76-81. doi: 10.1016/j.arbr.2015.12.012</mixed-citation><mixed-citation xml:lang="en">Suárez-Cuartín G, Crespo A, Mateus E, Torrejón M, Giner J, Belda A, et al. Variability in asthma inflammatory phenotype in induced sputum. Frequency and causes. Arch Bronconeumol. 2016; 52: 76-81. doi: 10.1016/j.arbr.2015.12.012</mixed-citation></citation-alternatives></ref><ref id="cit68"><label>68</label><citation-alternatives><mixed-citation xml:lang="ru">Panettieri RA Jr. Neutrophilic and pauci-immune phenotypes in severe asthma. Immunol Allergy Clin North Am. 2016; 36(3): 569-579. doi: 10.1016/j.iac.2016.03.007</mixed-citation><mixed-citation xml:lang="en">Panettieri RAJr. Neutrophilic and pauci-immune phenotypes in severe asthma. Immunol Allergy Clin North Am. 2016; 36(3): 569-579. doi: 10.1016/j.iac.2016.03.007</mixed-citation></citation-alternatives></ref><ref id="cit69"><label>69</label><citation-alternatives><mixed-citation xml:lang="ru">Kozik AJ, Huang YJ. The microbiome in asthma: Role in pathogenesis, phenotype, and response to treatment. Ann Allergy Asthma Immunol. 2019; 122(3): 270-275. doi: 10.1016/j.anai.2018.12.005</mixed-citation><mixed-citation xml:lang="en">Kozik AJ, Huang YJ. The microbiome in asthma: Role in pathogenesis, phenotype, and response to treatment. Ann Allergy Asthma Immunol. 2019; 122(3): 270-275. doi: 10.1016/j.anai.2018.12.005</mixed-citation></citation-alternatives></ref><ref id="cit70"><label>70</label><citation-alternatives><mixed-citation xml:lang="ru">Edwards MR, Strong K, Cameron A, Walton RP, Jackson DJ, Johnston SL. Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness. J Allergy Clin Immunol. 2017; 140(4): 909-920. doi: 10.1016/j.jaci.2017.07.025</mixed-citation><mixed-citation xml:lang="en">Edwards MR, Strong K, Cameron A, Walton RP, Jackson DJ, Johnston SL. Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness. J Allergy Clin Immunol. 2017; 140(4): 909-920. doi: 10.1016/j.jaci.2017.07.025</mixed-citation></citation-alternatives></ref><ref id="cit71"><label>71</label><citation-alternatives><mixed-citation xml:lang="ru">Adeli M, El-Shareif T, Hendaus MA. Asthma exacerbation related to viral infections: An up to date summary. J Family Med Prim Care. 2019; 8: 2753-2759. doi: 10.4103/jfmpc.jfmpc_86_19</mixed-citation><mixed-citation xml:lang="en">Adeli M, El-Shareif T, Hendaus MA. Asthma exacerbation related to viral infections: An up to date summary. J Family Med Prim Care. 2019; 8: 2753-2759. doi: 10.4103/jfmpc.jfmpc_86_19</mixed-citation></citation-alternatives></ref><ref id="cit72"><label>72</label><citation-alternatives><mixed-citation xml:lang="ru">Nair P, Aziz-Ur-Rehman A, Radford K. Therapeutic implications of ‘neutrophilic asthma’. Curr Opin Pulm Med. 2015; 21(1): 33-38. doi: 10.1097/MCP.0000000000000120</mixed-citation><mixed-citation xml:lang="en">Nair P, Aziz-Ur-Rehman A, Radford K. Therapeutic implications of ‘neutrophilic asthma’. Curr Opin Pulm Med. 2015; 21(1): 33-38. doi: 10.1097/MCP.0000000000000120</mixed-citation></citation-alternatives></ref><ref id="cit73"><label>73</label><citation-alternatives><mixed-citation xml:lang="ru">Panettieri RA. The role of neutrophils in asthma. Immunol Allergy Clin North Am. 2018; 38(4): 629-638. doi: 10.1016/j.iac.2018.06.005</mixed-citation><mixed-citation xml:lang="en">Panettieri RA. The role of neutrophils in asthma. Immunol Allergy Clin North Am. 2018; 38(4): 629-638. doi: 10.1016/j.iac.2018.06.005</mixed-citation></citation-alternatives></ref><ref id="cit74"><label>74</label><citation-alternatives><mixed-citation xml:lang="ru">Snelgrove RJ, Patel DF, Patel T, Lloyd CM. The enigmatic role of the neutrophil in asthma: Friend, foe or indifferent? Clin Exp Allergy. 2018; 48(10): 1275-1285. doi: 10.1111/cea.13191</mixed-citation><mixed-citation xml:lang="en">Snelgrove RJ, Patel DF, Patel T, Lloyd CM. The enigmatic role of the neutrophil in asthma: Friend, foe or indifferent? Clin Exp Allergy. 2018; 48(10): 1275-1285. doi: 10.1111/cea.13191</mixed-citation></citation-alternatives></ref><ref id="cit75"><label>75</label><citation-alternatives><mixed-citation xml:lang="ru">Nishio T, Wakahara K, Suzuki Y, Nishio N, Majima S, Nakamura S, et al. Mixed cell type in airway inflammation is the dominant phenotype in asthma patients with severe chronic rhinosinusitis. Allergol Int. 2019; 68(4): 515-520. doi: 10.1016/j.alit.2019.05.004</mixed-citation><mixed-citation xml:lang="en">Nishio T, Wakahara K, Suzuki Y, Nishio N, Majima S, Nakamura S, et al. Mixed cell type in airway inflammation is the dominant phenotype in asthma patients with severe chronic rhinosinusitis. Allergol Int. 2019; 68(4): 515-520. doi: 10.1016/j.alit.2019.05.004</mixed-citation></citation-alternatives></ref><ref id="cit76"><label>76</label><citation-alternatives><mixed-citation xml:lang="ru">Wakahara K, Nishio T, Suzuki Y, Majima S, Nakamura S, Hasegawa Y. Increasing sputum basophils is a marker for eosinophil-dominant airway inflammation in adult asthma. Eur Respir J. 2018; 52: PA4425. doi: 10.1183/13993003.congress-2018.PA4425</mixed-citation><mixed-citation xml:lang="en">Wakahara K, Nishio T, Suzuki Y, Majima S, Nakamura S, Hasegawa Y. Increasing sputum basophils is a marker for eosinophil-dominant airway inflammation in adult asthma. Eur Respir J. 2018; 52: PA4425. doi: 10.1183/13993003.congress-2018.PA4425</mixed-citation></citation-alternatives></ref><ref id="cit77"><label>77</label><citation-alternatives><mixed-citation xml:lang="ru">Ullmann N, Bossley CJ, Fleming L, Silvestri M, Bush A, Saglani S. Blood eosinophil counts rarely reflect airway eosinophilia in children with severe asthma. Allergy. 2013; 68: 402-406. doi: 10.1111/all.12101</mixed-citation><mixed-citation xml:lang="en">Ullmann N, Bossley CJ, Fleming L, Silvestri M, Bush A, Saglani S. Blood eosinophil counts rarely reflect airway eosinophilia in children with severe asthma. Allergy. 2013; 68: 402-406. doi: 10.1111/all.12101</mixed-citation></citation-alternatives></ref><ref id="cit78"><label>78</label><citation-alternatives><mixed-citation xml:lang="ru">Bossley CJ, Fleming L, Gupta A, Regamey N, Frith J, Oates T, et al. Pediatric severe asthma is characterized by eosinophilia and remodeling without T(H)2 cytokines. J Allergy Clin Immunol. 2012; 129: 974-982.e13. doi: 10.1016/j.jaci.2012.01.059</mixed-citation><mixed-citation xml:lang="en">Bossley CJ, Fleming L, Gupta A, Regamey N, Frith J, Oates T, et al. Pediatric severe asthma is characterized by eosinophilia and remodeling without T(H)2 cytokines. J Allergy Clin Immunol. 2012; 129: 974-982.e13. doi: 10.1016/j.jaci.2012.01.059</mixed-citation></citation-alternatives></ref><ref id="cit79"><label>79</label><citation-alternatives><mixed-citation xml:lang="ru">Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014; 43(2): 343-373. doi: 10.1183/09031936.00202013</mixed-citation><mixed-citation xml:lang="en">Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014; 43(2): 343-373. doi: 10.1183/09031936.00202013</mixed-citation></citation-alternatives></ref><ref id="cit80"><label>80</label><citation-alternatives><mixed-citation xml:lang="ru">Sagel SD, Wagner BD, Anthony MM, Emmett P, Zemanick ET. Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2012; 186: 857-865.</mixed-citation><mixed-citation xml:lang="en">Sagel SD, Wagner BD, Anthony MM, Emmett P, Zemanick ET. Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2012; 186: 857-865.</mixed-citation></citation-alternatives></ref><ref id="cit81"><label>81</label><citation-alternatives><mixed-citation xml:lang="ru">Jochmann A, Artusio L, Robson K, Nagakumar P, Collins N, Fleming L, et al. Infection and inflammation in induced sputum from preschool children with chronic airways diseases. Pediatr Pulmonol. 2016; 51(8): 778-786. doi: 10.1002/ppul.23366</mixed-citation><mixed-citation xml:lang="en">Jochmann A, Artusio L, Robson K, Nagakumar P, Collins N, Fleming L, et al. Infection and inflammation in induced sputum from preschool children with chronic airways diseases. Pediatr Pulmonol. 2016; 51(8): 778-786. doi: 10.1002/ppul.23366</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
